{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:12:55Z","timestamp":1772118775881,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100025799","name":"American Neuromuscular Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100025799","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS136683"],"award-info":[{"award-number":["R01NS136683"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>Therapeutic electrical stimulation (TES) shows promise in enhancing nerve regeneration, but outcomes vary widely. This study investigates the impact of the rs6265 single nucleotide polymorphism (SNP) on TES efficacy in a preclinical rat model and human stem cell\u2010derived motor neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Wild\u2010type (WT) and rs6265 variant rats underwent sciatic nerve transection and received either TES or sham treatment. Muscle reinnervation was assessed through compound muscle action potentials and muscle fiber cross\u2010sectional area. Isogenic human iPSC\u2010derived motor neurons were used to study activity\u2010dependent brain\u2010derived neurotrophic factor (BDNF) secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WT rats that received TES (WT Estim) showed improved muscle cross\u2010sectional area, electrophysiological muscle reinnervation, muscle fiber size, and NMJ reinnervation compared to Sham [\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0468,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0160,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001, respectively]. In contrast, rs6265 allele carriers did not experience a benefit of TES (rs6265 Estim) when compared to the Sham treatment [\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.9754,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.8606,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.9815,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.1047, respectively]. Additionally, rs6265 allele carriers exhibited impaired activity\u2010dependent BDNF secretion in\u00a0vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The rs6265 polymorphism influences TES efficacy, highlighting the need for personalized approaches in peripheral nerve injury (PNI) treatment. These findings suggest that genetic screening could optimize therapeutic outcomes. Understanding genetic factors affecting TES response can enhance treatment strategies for PNI, potentially improving patient recovery and reducing outcome variability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.28409","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T08:55:57Z","timestamp":1748336157000},"page":"149-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Impact of Brain\u2010Derived Neurotrophic Factor rs6265 (\n                    <scp>Val66Met<\/scp>\n                    ) Polymorphism on Therapeutic Electrical Stimulation for Peripheral Nerve Regeneration: A Preclinical Study of Therapy\u2013Genotype Interactions"],"prefix":"10.1002","volume":"72","author":[{"given":"Jordan B.","family":"Walters","sequence":"first","affiliation":[{"name":"Regenerative Neurorehabilitation Laboratory Shirley Ryan AbilityLab  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9120-4970","authenticated-orcid":false,"given":"Maria J.","family":"Quezada","sequence":"additional","affiliation":[{"name":"Regenerative Neurorehabilitation Laboratory Shirley Ryan AbilityLab  Chicago Illinois USA"},{"name":"Department of Biomedical Engineering Northwestern University  Evanston Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suning","family":"He","sequence":"additional","affiliation":[{"name":"Regenerative Neurorehabilitation Laboratory Shirley Ryan AbilityLab  Chicago Illinois USA"},{"name":"Department of Biomedical Engineering Northwestern University  Evanston Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciara S.","family":"Haynes","sequence":"additional","affiliation":[{"name":"Regenerative Neurorehabilitation Laboratory Shirley Ryan AbilityLab  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Steece\u2010Collier","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience College of Human Medicine, Michigan State University  Grand Rapids Michigan USA"},{"name":"Hauenstein Neuroscience Center Mercy Health Saint Mary's  Grand Rapids Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience College of Human Medicine, Michigan State University  Grand Rapids Michigan USA"},{"name":"Hauenstein Neuroscience Center Mercy Health Saint Mary's  Grand Rapids Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caryl E.","family":"Sortwell","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience College of Human Medicine, Michigan State University  Grand Rapids Michigan USA"},{"name":"Hauenstein Neuroscience Center Mercy Health Saint Mary's  Grand Rapids Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin K.","family":"Franz","sequence":"additional","affiliation":[{"name":"Regenerative Neurorehabilitation Laboratory Shirley Ryan AbilityLab  Chicago Illinois USA"},{"name":"Department of Physical Medicine and Rehabilitation Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Ken and Ruth Davee Department of Neurology Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Kimberly K. Querrey and Louis A. Simpson Institute for Bioelectronics Northwestern University  Evanston Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59320"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-07-02602.2000"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06631.2002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40463-017-0244-9"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.09.020"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyz322"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24397"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.130094"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00012"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0127-1"},{"key":"e_1_2_11_12_1","volume-title":"rs6265 Reference SNP (rs) Report","year":"2022"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19159732"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.24"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00156"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2000.01341.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.01.040"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00522"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105175"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270892"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/360755a0"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/360757a0"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1545968319846131"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1545968307313502"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.02.013"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.05.034"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21912"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154243"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep09669"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23148011"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-31703-8"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480230107"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.07049.x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1399-10.2011"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180585"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/1545968314542617"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.28409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T03:18:56Z","timestamp":1749093536000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.28409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,21]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/mus.28409"],"URL":"https:\/\/doi.org\/10.1002\/mus.28409","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.08.29.610333","asserted-by":"object"}]},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,21]]},"assertion":[{"value":"2024-08-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}